Navigation Links
Brain size may depend upon how neural cells are cleaved

Howard Hughes Medical Institute researchers have discovered a novel way in which the brain size of developing mammals may be regulated. They have identified a signaling pathway that controls the orientation in which dividing neural progenitor cells are cleaved during development.

The way these cells are sliced during development is critical because at later stages of neurogenesis, vertical cleavage gives rise to two mature neurons that are incapable of further division, while horizontal cleavage yields one neuron and one progenitor cell that can continue to support brain growth.

The researchers speculate that this type of regulatory decision point may play a powerful role in determining the ultimate size of the mammalian brain. Inherited disorders that cause the brain to develop too small or too large may also influence this developmental pathway.

Howard Hughes Medical Institute investigator Li-Huei Tsai and postdoctoral fellow Kamon Sanada, both at Harvard Medical School, published their findings in the July 15, 2005, issue of the journal Cell.

The researchers drew on studies by other researchers that showed that the orientation of cleavage planes in dividing neural progenitor cells in the neocortex determines the fate of the resulting daughter cells. However, nothing was known about the molecular signaling mechanism that regulates the decision to cleave one way or another, said Tsai.

Studies in fruit flies and roundworms had hinted that major regulatory molecules called heterotrimeric G proteins play a role in orienting the mitotic spindles that govern the orientation of cell cleavage during cell division, or mitosis.

"Based on that knowledge, we knew that heterotrimeric G proteins were very good candidates as regulators of the plane of cell division in neural precursors," said Tsai.

"And this is a very important question, because how these cells divide ultimately determines the final number of cells that will be generated during brain development," she said.

Using the embryonic mouse brain as a model, Sanada and Tsai sought to determine whether G proteins play a role in the developing mammalian brain. In their initial experiments, they impaired the function of the Gβγ subunits of heterotrimeric G proteins, in the developing mouse brain. They saw a dramatic interference with orientation of cell cleavage to overproduce "postmitotic" neurons -- cells that could no longer divide -- at the expense of progenitor cells, which could still divide. "This observation led us to want to further test whether impairment of Gβγ has any consequences for cell fate in division, because it has been speculated that the different division planes dictate the ultimate cell fate adoption of daughter cells," said Tsai.

To determine definitively whether impairment of Gβγ had a direct effect on cell fate, the researchers impaired Gβγ signaling in the mouse brains in utero, then isolated the progenitor cells to study the effects in vitro. Those studies revealed that impairing Gβγ did result in overproduction of neurons as a result of both daughter cells adopting the neuronal fate. Thus, the researchers concluded that Gβγ does control the orientation of cleavage and the identity of the daughter cells -- whether they will become neurons or progenitor cells.

Sanada and Tsai also sought to determine how Gβγ is regulated. Studies on asymmetric cell division in fruit flies and roundworms had implicated a particular class of proteins -- known as AGS3 and mPins in mammals -- as upstream regulators of G proteins.

The researchers' analyses showed that AGS3 is, indeed, expressed in progenitor cells. And when they "silenced" AGS3 expression in embryonic mouse brains, the resulting abnormalities mimicked those produced when Gβγ signaling was disrupted.

Now that the role of Gβγ in neural cell proliferation has been discovered, said Tsai, further studies will try to pinpoin t how its signaling determines the orientation of spindles during mitosis, and thus the orientation of cell cleavage.

"While this is basic research, we do know that this mechanism is very important in determining the ultimate size of the brain," said Tsai. "And, there are humans born with too few neurons, called microcephaly, or too many neurons, called macrocephaly. I would speculate that many of these cases are the outcome of some sort of impairment in the regulation of cell division, perhaps in the plane of division," said Tsai.

"And with the possibility that neural stem cells may find therapeutic use, the role of G protein signaling in the differentiation of such progenitor cells is going to be a very exciting area to explore," she said.


'"/>

Source:Howard Hughes Medical Institute


Related biology news :

1. Drug That Tags Decision-making Areas Of The Brain May Aid
2. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
3. Transport System Smuggles Medicines Into Brain
4. Bird Brains Show How Trial and Error May Contribute to Learning
5. VCU Researchers Identify Networks Of Genes Responding To Alcohol In The Brain
6. Wiley announces publication of Databasing the Brain
7. Scientists Propose Sweeping Changes to Naming of Bird Neurosystems to Acknowledge Their True Brainpower
8. Brain-mapping technique aids understanding of sleep, wakefulness
9. Some Brain Cells Change Channels To Fine-tune The Message
10. Brain Scans Reveal How Gene May Boost Schizophrenia Risk
11. Brain-injury rehabilitation depends on acetylcholine circuitry
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/29/2016)... 2016   Neurotechnology , a provider ... technologies, today released FingerCell 3.0, a software ... that run on low-power, low-memory microcontrollers. FingerCell ... than 128KB of memory, enabling it to ... limited on-board resources, such as: mobile phones, ...
(Date:11/22/2016)... 2016 According to the new market research report ... Vein, Signature, Voice), Multi-Factor), Component (Hardware and Software), Function (Contact and Non-contact), ... market is expected to grow from USD 10.74 Billion in 2015 to ... 2016 and 2022. Continue Reading ... ...
(Date:11/17/2016)... , Nov. 17, 2016 Global Market Watch: ... Biobanks (Disease-Based Banks, Population-Based Banks and Academics) market is to ... for Private Biobanks shows the highest Compounded Annual Growth Rate ... region during the analysis period 2014-2020. North ... of 9.95% followed by Europe at ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... OXFORD, England , December 8, 2016 /PRNewswire/ ... (OGT), das Unternehmen für Molekulargenetik, erweitert seine Palette ... SureSeq myPanel™ NGS Custom FH Panels, das ein ... Hypercholesterinämie (FH) ermöglicht. Das Panel bietet eine Erkennung ... Number Variations (CNV) mit einem einzigen kleinen Panel ...
(Date:12/8/2016)... ... December 08, 2016 , ... KBioBox ... response to client demand KbioBox developed a sophisticated “3 click” gene dditing off ... accessible from KBioBox’s new website, https://www.kbiobox.com/ and powered by the ...
(Date:12/8/2016)... ... ... This CAST literature review and report looks at problems caused by the current ... in countries that are major global commodity exporters and importers, which show that asynchrony ... level presence (LLP) puts large volumes of trade worth billions of dollars at risk. ...
(Date:12/8/2016)... TAMPA, Fla. , Dec. 8, 2016 /PRNewswire/ ... biopharmaceutical company that discovers, develops and plans to ... today that its shares of common stock were approved ... stock will begin trading on the OTCQX, effective ... To qualify for the OTCQX market, companies must ...
Breaking Biology Technology: